Increased lipogenesis and fatty acid reesterification contribute to hepatic triacylglycerol stores in hyperlipidernic Txnip-/- mice
Increased lipogenesis and fatty acid reesterification contribute to hepatic triacylglycerol stores in hyperlipidernic Txnip-/- mice
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DOI：
10.1093/jn/134.6.1475
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发表时间：
2004-06-01
影响因子：
4.2
通讯作者：
Parks, EJ
中科院分区：
文献类型：
--
作者：
Donnelly, KL;Margosian, MR;Parks, EJ
采用代谢标记法研究了脂肪酸氧化降低对高脂血症小鼠模型HcB-19小鼠（Txnip(-/-)）肝脏脂质代谢的影响。用1- c -13(1)乙酸定量新胆固醇合成和新脂肪生成，用三己酸甘油酯-d（31）定量从膳食脂肪酸中提取的肝脏三酰基甘油（TAG）。组织样品分析TAG、游离胆固醇（FC）和胆固醇酯（CE）含量。与野生型（WT）相比，Txnip（-/-）小鼠血清非酯化脂肪酸显著升高（P < 0.05）；他们的肝脏更重，含有更多的TAG和总胆固醇。Txnip（-/-）肝脏也含有可测量的CE；在WT小鼠中未检测到CE。肝脏CE含量升高，尽管胆固醇分数合成率较低（Txnip（-/-）和WT小鼠分别为16%和31% /d）。WT小鼠的FC绝对合成率（ASR）为0.28 +/- 0.0 mumol/d, Txnip（-/-）小鼠的FC合成率（0.13 +/- 0.10 mumol/d）和CE合成率（0.10 +/- 0.00 mumol/d）相似。根据tag -棕榈酸ASR评估，Txnip（-/-）小鼠的脂肪生成显著增加（1.47 +/- 0.08 vs. 0.49 +/- 0.06 mumol/d），肝脏脂肪酸合成酶活性也更高（7,96 +/- 2.53 vs. 4.83 +/- 1.44 U/mg蛋白）。Txnip（-/-）小鼠肝脏脂肪生成和脂肪酸再酯化成甘油和胆固醇的增加。这些数据支持脂肪酸合成升高是Txnip（-/-）小鼠肝脏TAG的主要因素，尽管脂肪酸酯化增加也导致肝脏TAG过量。绝对总胆固醇合成速率没有改变，但脂肪酸酯化成胆固醇提供了一种额外的手段，从生理上缓冲过量脂肪酸可用性的负面结果。
The effect of decreased fatty acid oxidation on liver lipid metabolism in HcB-19 mice, a mouse model of hyperlipidemia (Txnip(-/-)), was investigated using metabolic labeling. De novo cholesterol synthesis and de novo lipogenesis were quantified using 1-C-13(1) acetic acid, and liver triacylglycerol (TAG) derived from dietary fatty acids was quantified using dietary glyceryl tri(hexandecanoate-d(31)). Tissue samples were analyzed for TAG, free cholesterol (FC), and cholesterol ester (CE) content. Txnip(-/-) mice had significantly elevated (P < 0.05) serum nonesterified fatty acids compared with wild-type (WT) littermates; their livers weighed more and contained more TAG and total cholesterol. Txnip(-/-) liver also contained measurable CE; CE was not detectable in WT mice. Liver CE content was elevated despite lower cholesterol fractional synthesis rates (16 vs. 31 %/d in Txnip(-/-) and WT mice, respectively). FC absolute synthesis rate (ASR) in WT mice (0.28 +/- 0.0 mumol/d) was similar to the combined synthesis rates of FC (0.13 +/- 0.10 mumol/d) and CE (0.10 +/- 0.00 mumol/d) in Txnip(-/-) mice. Lipogenesis, as assessed by TAG-palmitate ASR, was significantly greater in Txnip(-/-) mice (1.47 +/- 0.08 vs. 0.49 +/- 0.06 mumol/d) and liver fatty acid synthase activity was also higher (7,96 +/- 2.53 vs. 4.83 +/- 1.44 U/mg protein). Both elevated lipogenesis and increased fatty acid reesterification to glycerol and cholesterol contributed to fat in the livers of Txnip(-/-) mice. These data support elevated fatty acid synthesis as the primary contributor to liver TAG in Txnip(-/-) mice, although increased esterification of fatty acids also contributed to excess liver TAG. The absolute total cholesterol synthesis rate was not altered, but esterification of fatty acids to cholesterol provided an additional means to buffer physiologically the negative results of excess fatty acid availability.